DESCRIPTION (As Adapted from the Investigator's Abstract): Light chain-associated amyloidosis (AL amyloidosis) is a plasma cell dyscrasia characterized by the systemic fibrillar deposition of monoclonal light chains and related fragments; the resultant pathology leads to progressive organ dysfunction and eventual death. Heretofore, therapeutic efforts in this disease have been directed towards reducing by conventional or high-dose cytotoxic chemotherapy the synthesis of the amyloidogenic precursor light chain. The recent serendipitous discovery in Europe that the iodinated anthracycline 4'-iodo-4'-deoxydoxorubicin-I-DOX-can in certain patients effect resorption of amyloid deposits has provided another treatment approach to be tested in a Phase II clinical trial involving three amyloid centers in the United States. The protocol also includes a research arm that has as its overall objective the characterization, using highly sensitive methodology, of the chemical features of AL fibrils extracted from sections of formalin-fixed, paraffin-embedded tissue or fat biopsies. The ultimate goal of this work is to identify factors that may presage response to I-DOX therapy. This study will also provide the opportunity to determine the clinical efficacy of our newly developed assay systems that are based on the amount of Congophilic material contained in subcutaneous fat as markers of amyloid burden pre- and post-treatment. The three specific aims of the proposed research are designed to test our hypotheses that such information has diagnostic and prognostic import and are as follows: 1) to establish unequivocally the nature of the amyloid deposits in patients entered on the I-DOX study; 2) to ascertain if particular chemical or other phenotypic properties of AL amyloid deposits affect response to I-DOX therapy; and 3) to determine the therapeutic and prognostic utility of qualitative and quantitative assays of AL amyloid deposition in patients treated with I-DOX. This exploratory Grant for Correlative Laboratory Studies and Clinical Trials (PAR-96-040) application is designed to provide an essential research component to the I-DOX protocol that will result in new knowledge on the pathogenesis of AL amyloidosis. The ultimate goal of the proposed studies is to improve the prognosis of patients with this fatal disease.